The Interplay Between Inborn Error of Immunity and Blood Disorders: Unravelling Immune Defects Behind Common Haematological Diseases

NCT06857604 | Recruiting

• 1 other identifier: IEI-Haem
• Study Type: interventional
• Target: 700
• Locations: 5 countries
• Sites: 7

Brief Summary

The universe of Inborn errors of Immunity (IEI) is rapidly expanding: their clinical spectrum is not only characterised by infections but often includes haematological complications. Moreover, an increasing number of "IEI phenocopies" due to somatic mutations in specific cell types are progressively being unveiled and complicate the genetic plot of IEI, which are therefore not only caused by germline mutations. However, these aspects have never been studied by large prospective studies. This study aims to fill this gap by prospectively recruiting patients \<25 y/o with haematologic disorders that fall into one of the following 4 subgroups: autoimmune cytopenia (AICs), polyclonal lymphoproliferation (PL), monoclonal (malignant) lymphoproliferation (ML), bone marrow failure/myelodysplasia (BMF/MDS). Recruited subjects will undergo an extensive immunologic workup (extended immunophenotyping, cytokine and autoantibody dosage) together with genetic testing (NGS) to detect both germline and somatic variants. Bulk RNA sequencing will be performed either as functional validation of variants or to identify altered pathways in selected cases with inconclusive genetics. Patient advocacy organisations (PAOs) will be pivotal to assist patients' needs throughout the project and to raise awareness of predictive and yet unknown signs of IEI. The study involves recruitment a total of almost 700 children over a 3-year period. Considering recent studies on AICs and BMF/MDS, a global detection rate of 30% "hidden" IEI is expected, with higher rates in the AIC subgroup and lower ones for ML, given the complexity of lymphoma pathogenesis. New IEI candidate genes or new examples of IEI phenocopies are expected to be identified. The immunological workup should detect early disease biomarkers or currently unknown molecular signatures of specific disorders. These may increase the chance of identifying an IEI in a specific subgroup and promptly address the patient to a targeted treatment or to hematopoietic stem cell transplantation, avoiding late complications, increasing patients' survival, and abating the economic burden of the disease on healthcare services. Finally, involvement of PAOs may foster patients' knowledge about their condition, increasing their compliance to disease follow-up and treatment and ameliorating their quality of life.

Conditions

Hematologic Diseases

Outcome Measures

Primary Outcomes (1)

• Number of children and young adults with blood disorders with new or known germline and somatic mutations that cause or modify disease, either in the lymphoid or myeloid compartments.

  From enrollment to the end of analysis (36 months)

Secondary Outcomes (1)

• Percentage of pediatric and adolescent-young adult patients with hematologic disorders with altered immunological profiles

  From enrollment to the end of analysis (36 months)

Study Arms (1)

Patients with Haematological Disorders

OTHER

Patients with diagnosed autoimmune cytopenias (AIC), polyclonal lymphoproliferation (PL), lymphoma (ML), bone marrow failure, and myelodysplastic syndrome (BMF/MDS)

Other: Biological samples

Interventions

Biological samples OTHER

Immunological Screening and Genetic analysis

Patients with Haematological Disorders

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients age \< 25 years
• Patients with diagnosed autoimmune cytopenias (AIC), polyclonal lymphoproliferation (PL), lymphoma (ML), bone marrow failure, and myelodysplastic syndrome (BMF/MDS) (see details below)
• Signed Informed Consent

You may not qualify if:

• Patients with Lymphoma secondary to HIV or transplant
• Patient with self-resolving or post-infective AICs

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (7)

CHU Sainte-Justine

Montreal, Canada, Canada

RECRUITING

CHU Sainte-Justine

Montreal, Canada, Canada

RECRUITING

Institut Imagine

Paris, France, France

RECRUITING

Meyer Children's Hospital IRCCS, Firenze

Florence, Fi, 50139, Italy

RECRUITING

University of Rome Tor Vergata

Rome, Italy, Italy

RECRUITING

Vall d'Hebron Institut de Recerca

Barcelona, Spain

RECRUITING

Karolinska Institutet

Stockholm, Sweden, Sweden

RECRUITING

MeSH Terms

Conditions

Hematologic Diseases

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Central Study Contacts

Eleonora Gambineri, MD

CONTACT

+390555662624; eleonora.gambineri@meyer.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: March 4, 2025
• Study Start: November 15, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); FR (1); IT (2); CA (2); ES (1)